SCOPE: Diagnosis and management of parkinsonism (tremor, rigidity, bradykinesia, postural instability) caused by dopamine-blocking or dopamine-depleting medications. Covers identification of causative agents, differentiation from idiopathic Parkinson's disease, medication discontinuation/substitution strategies, symptomatic treatment, and psychiatric collaboration for patients requiring continued antipsychotic therapy. Excludes idiopathic Parkinson's disease (separate protocol), vascular parkinsonism, atypical parkinsonian syndromes (PSP, MSA, CBD, DLB), neuroleptic malignant syndrome (acute management), and tardive dyskinesia (separate protocol).
DEFINITIONS:
- Drug-Induced Parkinsonism (DIP): Parkinsonism caused by medications that block or deplete dopamine, typically presenting within days to months of exposure
- Parkinsonism: Clinical syndrome of bradykinesia plus at least one of: rest tremor, rigidity, or postural instability
- Bradykinesia: Slowness of movement with progressive reduction in speed and amplitude with repetitive actions
- Rest Tremor: 4-6 Hz tremor present at rest, suppressed with action (may be less prominent in DIP than idiopathic PD)
- Dopamine Receptor Blocking Agent (DRBA): Medications that antagonize D2 dopamine receptors (antipsychotics, antiemetics)
- DaTscan: Dopamine transporter imaging used to differentiate DIP (normal uptake) from idiopathic PD (reduced uptake)
- :: - :: - :: Immediate discontinuation if not psychiatrically required; gradual taper over 1-2 weeks if on antipsychotic to avoid withdrawal psychosis
Active psychosis requiring continued antipsychotic (coordinate with psychiatry)
Do not restart the discontinued medication without neurology approval as this will likely cause parkinsonism recurrence
STAT
STAT
ROUTINE
Return immediately if new-onset high fever, severe rigidity, altered consciousness, or autonomic instability develops (may indicate neuroleptic malignant syndrome)
STAT
STAT
ROUTINE
Report any new tremor, stiffness, slowness, or balance problems that develop after starting any new medication to your physician promptly
ROUTINE
ROUTINE
ROUTINE
Symptoms may take weeks to months to fully resolve after stopping the causative medication; improvement is expected but gradual
-
ROUTINE
ROUTINE
Do not take over-the-counter antiemetics containing metoclopramide, prochlorperazine, or promethazine without physician approval as these can cause parkinsonism
ROUTINE
ROUTINE
ROUTINE
Inform all healthcare providers of your history of drug-induced parkinsonism so dopamine-blocking agents are avoided in the future
ROUTINE
ROUTINE
ROUTINE
Use fall precautions including assistive devices, non-slip footwear, and removal of home hazards due to balance and gait impairment
-
ROUTINE
ROUTINE
If parkinsonian symptoms do not improve within 3-6 months of drug withdrawal, return for re-evaluation as this may indicate underlying Parkinson's disease
Fall prevention measures including grab bars, non-slip mats, adequate lighting, and removal of loose rugs due to postural instability and gait impairment
-
ROUTINE
ROUTINE
Regular low-impact exercise (walking, tai chi, swimming) to maintain mobility and reduce stiffness from parkinsonian rigidity
-
ROUTINE
ROUTINE
Maintain medication allergy/adverse reaction list updated with all dopamine-blocking agents that caused parkinsonism for future reference
ROUTINE
ROUTINE
ROUTINE
Avoid alcohol which may exacerbate balance problems and interact with medications used for symptom management
-
ROUTINE
ROUTINE
Adequate nutrition and hydration to support neurologic recovery and prevent orthostatic hypotension
-
ROUTINE
ROUTINE
Home safety evaluation by occupational therapy to identify environmental hazards and recommend adaptive equipment
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ROUTINE
ROUTINE
MedAlert bracelet or wallet card noting drug-induced parkinsonism and specific agents to avoid for emergency situations
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-
ROUTINE
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SECTION B: REFERENCE (Expand as Needed)
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Mild parkinsonism; causative agent identified and discontinued/substituted; outpatient neurology follow-up arranged within 2-4 weeks; no concern for NMS; patient/family educated on medication avoidance
Admit to floor
Severe parkinsonism causing functional impairment (unable to ambulate safely, unable to perform ADLs); need for psychiatric medication adjustment requiring close observation; complex medication reconciliation requiring pharmacy and multidisciplinary input; concern for diagnostic uncertainty requiring inpatient workup
Admit to ICU
Suspected neuroleptic malignant syndrome (fever, severe rigidity, autonomic instability, altered consciousness); severe dysphagia with aspiration risk; inability to protect airway; hemodynamic instability
Transfer to higher level
Diagnostic uncertainty requiring movement disorders specialist not available at current facility; suspected NMS requiring critical care not available locally
Discharge from hospital
Parkinsonism stabilized or improving; psychiatric medications adjusted with stable mental status for 48-72 hours; safe ambulation with or without assistive device; outpatient follow-up arranged with neurology and psychiatry; patient/family educated on medication avoidance
v1.1 (January 30, 2026)
- Standardized all structured dosing to 4-field :: delimited format (dose :: route :: frequency :: full_instructions) per C1/M1/R3
- Split Benztropine into separate PO (maintenance) and IM/IV (acute) rows for correct route-specific dosing per M3
- Split Diphenhydramine into separate IV/IM (acute) and PO (maintenance) rows for correct route-specific dosing per M3
- Split Ondansetron into separate IV (acute) and PO (maintenance) rows for correct route-specific dosing per M3
- Added ICU coverage for core labs (CBC, CMP, glucose, drug levels, medication reconciliation) relevant to NMS workup per S1/R4
- Added ICU coverage for extended labs (CK, valproic acid level, lithium level) per S1/R4
- Added ICU STAT coverage for Section 3A causative agent management (all 4 interventions) per S2
- Added ICU coverage for ondansetron IV (STAT) and psychiatric status monitoring (URGENT) per S2
- Added ICU URGENT for psychiatry consult and ROUTINE for pharmacy consult in Section 4A per S1
- Added ICU URGENT for psychiatric status monitoring in Section 6 per S1
- Added medication timeline review ICU = STAT per S2
- Used - :: - :: - :: format for non-medication intervention rows (discontinuation/taper orders) per M2
- Added ═══ section dividers before Section B header per R1/R5
- Added PubMed citation links to all 21 references in Section 8 per R2
- Corrected Ward KM citation co-author from "Bhatt DL" to "Citrome L" per accuracy check
- Added CrCl <15 contraindication detail to amantadine dosing instructions
- Updated version to 1.1 and added REVISED date
v1.0 (January 30, 2026)
- Initial template creation
- Comprehensive coverage of DIP diagnosis, causative agents, and differentiation from idiopathic PD
- Detailed medication management including discontinuation strategies and psychiatric substitution
- DaTscan and advanced imaging guidance for diagnostic uncertainty
- Anticholinergic and amantadine symptomatic treatment with structured dosing
- Alternative antipsychotic substitution guidance (quetiapine, clozapine, aripiprazole)
- Non-dopaminergic antiemetic substitution (ondansetron, domperidone)
- Causative agent reference table with risk stratification
- Key distinguishing features table for DIP vs idiopathic PD
- 21 evidence-based references
APPENDIX A: Causative Agent Risk Stratification and Substitution Guide¶
High-Risk Agents (Discontinue or Substitute Immediately):
Causative Agent
Recommended Substitute
Notes
Haloperidol
Quetiapine or clozapine
Coordinate with psychiatry; haloperidol has highest EPS risk
Chlorpromazine
Quetiapine or aripiprazole
Lower-potency typical but still significant EPS risk
Fluphenazine (including decanoate)
Quetiapine or clozapine
Decanoate formulation: effects persist weeks after last injection
Risperidone (>4 mg/day)
Quetiapine, aripiprazole, or reduce to <4 mg/day
EPS risk is dose-dependent
Metoclopramide
Ondansetron (antiemetic); erythromycin or domperidone (prokinetic)
FDA black box warning for prolonged use
Prochlorperazine
Ondansetron or meclizine
Common ER prescription for nausea/vertigo
Moderate-Risk Agents (Reduce Dose or Monitor Closely):
Causative Agent
Recommended Action
Notes
Olanzapine
Reduce dose; consider switch to quetiapine
EPS less common than typicals but dose-related
Valproate
Reduce to therapeutic minimum; consider alternative mood stabilizer
Parkinsonism typically reversible with dose reduction
Lithium
Check level; reduce to minimum therapeutic
Toxicity increases EPS risk
Flunarizine/cinnarizine
Discontinue; substitute alternative migraine prophylaxis
When to Order DaTscan:
- Diagnostic uncertainty between DIP and idiopathic PD
- Parkinsonism persists >6 months after causative agent withdrawal
- Atypical features suggesting underlying neurodegenerative process
- Patient requires urgent diagnostic clarification (e.g., before surgery)
Interpretation:
DaTscan Result
Interpretation
Clinical Action
Normal bilateral striatal uptake
Supports pure DIP; presynaptic dopamine neurons intact
Continue observation; expect resolution after drug withdrawal; reassess in 3-6 months
Reduced striatal uptake (asymmetric)
Suggests underlying idiopathic PD unmasked by DRBA
Refer to movement disorders specialist; consider levodopa trial; DIP may have unmasked subclinical PD
Reduced striatal uptake (symmetric)
May indicate PD or atypical parkinsonism unmasked by DRBA
Movement disorders specialist; further workup for atypical parkinsonism
Medications That Interfere with DaTscan (Hold Before Study):
- Bupropion (hold 2 weeks)
- Amphetamines/methylphenidate (hold 2 weeks)
- Modafinil (hold 2 weeks)
- Cocaine (hold 2 weeks)
- Phentermine (hold 2 weeks)
- Benztropine and anticholinergics do NOT interfere
DaTscan Does NOT Differentiate Between:
- PD and atypical parkinsonism (PSP, MSA, CBD) - all may show reduced uptake
- PD subtypes (tremor-dominant vs PIGD)
APPENDIX C: DIP Resolution Timeline and Follow-Up Protocol¶
Expected Resolution Timeline After Drug Withdrawal:
Timeframe
Expected Clinical Course
Action
Week 1-2
Minimal change; may initially worsen slightly after antipsychotic withdrawal
Reassure patient; monitor psychiatric status
Week 2-4
Early improvement in bradykinesia and rigidity expected
Continue symptomatic treatment if needed
Month 1-3
Significant improvement in most patients; tremor may be last to resolve
Consider tapering symptomatic medications
Month 3-6
Full resolution expected in most patients
If persistent, order DaTscan
Month 6-12
Any residual symptoms raise concern for underlying PD
Movement disorders referral; levodopa trial
>12 months
Persistent parkinsonism highly suggests underlying PD unmasked by DRBA
Manage as idiopathic PD
Follow-Up Schedule:
1. 2 weeks post-discontinuation: Psychiatric status, initial motor assessment, medication review
2. 4 weeks post-discontinuation: Motor re-examination, UPDRS scoring, assess functional improvement
3. 3 months post-discontinuation: Comprehensive motor assessment; if not improving, order DaTscan
4. 6 months post-discontinuation: Final assessment; if fully resolved, educate on future medication avoidance
5. As needed: If symptoms recur or new medications started